The interrelationship of alcohol and the pituitary-adrenocortical and pituitary-gonadal systems will be studied in laboratory mice and rats from a developmental and behavior genetic perspective. The responsiveness of the pituitary-adrenocortical system during the prolonged alcohol intoxication and withdrawal phase will be studied by correlating the changes in the endocrine responsiveness to alcohol and other stressors with the concentration of the steroid in different brain regions of the rat. This approach may provide an animal model of the pituitary-adrenocortical non-responsiveness to alcohol stress observed in some human alcoholics which shares certain similarities with patients under chronic glucocorticoid treatment. The corticosterone in blood and brain tissue will be assayed fluorometrically after the chromatographic separation of the steroid. (During the initial phase of the project, a serious effort will be made to make protein-binding assay of corticosterone workable in the laboratory.) The effect of prenatal exposure to alcohol (via intoxicating the mothers) upon the development of the pituitary axis during the last stage of fetal period (Days 18-21 gestation) and during the first three weeks of neonatal period. During the fetal period, the main index of the endocrine development will be the weight of the adrenal gland in relation to fetal weight and also in relation to the corticosteroid levels of the gestating females. During the postnatal period, the basal and stress levels of plasma and brain corticosterone, in addition to the general growth and development, will be determined and compared with the normal values for the stress-non-responsiveness period. Furthermore, the hypothesis to be tested is that the developmental anomalies described as "fetal alcohol syndrome," including CNS and skeletal dismorphogeneses involve similar teratogenic mechanisms as corticosteroid-induced developmental abnormalities which are well documented in various strains of mice. The effect of alcohol administration upon the initial phase of pregnancy will be studied in several inbred strains of mice known to differ in sensitivity to alcohol by examining implantation of fertilized eggs and the number of viable fetuses.